Porphyria

This research investigates the use of a carbohydrate-rich diet as a treatment for acute intermittent porphyria (AIP), a genetic condition causing buildup of porphobilinogen leading to severe symptoms like abdominal pain, paralysis, fatigue, inflammation, and increased risk of kidney and liver problems. The study aims to understand how different carbohydrate levels impact tissue and serum glucose, insulin, inflammatory markers, amino acids, gut bacteria, mitochondrial activity, and genetic markers in AIP patients. Researchers will explore how these factors relate to AIP symptoms and overall health. Participants will follow two diet plans in a randomized crossover design: one with 60-65% of energy from carbohydrates and another with 40-45% carbohydrates, each lasting four weeks with a four-week washout period between. Half of the participants start with the higher carbohydrate diet and then switch to the lower, while the other half do the reverse. Nutritional plans meet recommended guidelines to maintain stable weight. The study is conducted by multiple institutions, including Nordland Hospital and the University of Oslo, with expert teams developing diets and analyzing results. During the study, participants will have various assessments including urine tests for porphobilinogen, blood and tissue glucose levels, insulin, cytokines, amino acids, gut microbiota, physical activity, body composition, blood pressure, and mitochondrial function. These measures are taken before and after each diet period, with continuous glucose monitoring and physical activity tracking using devices. Researchers will also analyze genetic markers linked to energy metabolism. The total participation includes two four-week diet periods separated by a washout, with detailed monitoring throughout.

Researchers are conducting a global patient registry to better understand the natural history and real-world clinical management of patients with Acute Hepatic Porphyria (AHP). This observational study also aims to gather information on the real-world safety and effectiveness of givosiran and other approved treatments for AHP. The registry is sponsored by Alnylam Pharmaceuticals and includes patients diagnosed with AHP. Participants with AHP will be enrolled and managed according to their usual clinical care without any assigned interventions by the study. The study collects data over time to observe how patients are treated in routine practice and how their condition progresses. There are no experimental treatments given as part of this registry. During the study, researchers will track the occurrence of selected events of interest related to AHP for up to six years. They will also monitor the annual rate of porphyria attacks and assess patients' quality of life using the 12-Item Short Form Health Survey Version 2. Participants will be followed prospectively to provide ongoing information about their health and treatment outcomes.

Researchers are investigating the genetic factors that may influence acute attacks in people with Acute Intermittent Porphyria (AIP), a hereditary disorder affecting heme production. The study aims to identify specific genes that may increase or decrease the risk of these attacks in symptomatic patients. This observational study is sponsored by the Icahn School of Medicine at Mount Sinai. Participants include symptomatic patients with AIP who have experienced acute attacks, as well as their family members who carry AIP mutations or are related to affected individuals. The study involves collecting blood, saliva, and urine samples along with clinical information to analyze genetic variants. There are no treatments or interventions being tested, as this study focuses on genetic observation. During the study, participants provide biological samples and medical history for analysis. Researchers will measure the odds ratios of how identified modifier genes or variants affect the occurrence of acute attacks. The study involves ongoing data collection and genetic analysis until June 2026. Participation requires informed consent and willingness to provide samples and information.

This research aims to study a group of rare metabolic diseases called porphyrias, which can appear in childhood or adulthood due to enzyme deficiencies affecting heme production. These diseases often cause acute neurological attacks or skin sensitivity to light. Because diagnosis is often delayed and the natural course of these diseases is not well understood, the study seeks to better understand disease progression, complications, pregnancy outcomes, and mortality, as well as the effects of current treatments and the development of new therapies. The study includes patients with confirmed diagnoses of various types of porphyrias, such as Acute Intermittent Porphyria, Hereditary Coproporphyria, Variegate Porphyria, and others. It is a long-term observational study conducted by a consortium of academic centers funded by the NIH. Participants are grouped based on their specific porphyria diagnosis and will be followed over time to collect clinical, biochemical, and genetic data. Participants will provide information through clinical evaluations and laboratory tests, including biochemical and genetic studies, at baseline and throughout the study. Researchers will assess disease severity, biomarkers, and treatment effectiveness and tolerability. The study monitors participants over an extended period to gather detailed information about the natural history and outcomes associated with porphyrias. This may include gathering data on complications and pregnancy outcomes. The total participation duration varies by individual.

This research aims to collect detailed information about the effects of Erythropoietic Protoporphyria (EPP) and X-Linked Porphyria (XLP) in adolescents and adults. It is an observational study, meaning participants will not receive any treatment while researchers observe and record their symptoms and related health data. The study is conducted to better understand these rare conditions and how they affect participants over time. Participants will be involved in the study for up to 6 months, starting with a screening and a baseline visit on Day 1. After that, they will return every 4 weeks for follow-up visits through 24 weeks. During these visits, researchers will perform clinical laboratory tests, physical exams, vital sign measurements, and blood draws to measure protoporphyrin IX (PPIX) levels. Participants will also wear a light dosimetry device to monitor light exposure and complete daily diaries reporting their symptoms. Throughout the study, participants will be assessed for phototoxic symptoms, skin damage, and sunlight exposure required to trigger symptoms. Data collection includes clinical history, symptom timing, liver function tests, and light exposure records. The study team monitors participants’ health during each visit to understand the progression and impact of EPP/XLP, with no treatment administered as part of this research.

Researchers are evaluating the effectiveness of 5-aminolevulinic acid hydrochloride (5-ALA HCl) fluorescence-guided microsurgery compared to conventional white light microsurgery in patients with malignant gliomas (WHO grade 3/4). This phase III, randomized, open, parallel-group, multicenter study aims to assess how well these two surgical methods remove tumor tissue safely. Participants are randomly assigned to either the test group or the control group in equal numbers. The test group receives an oral dose of 5-ALA HCl at 20 mg/kg dissolved in drinking water 2 to 4 hours before anesthesia, followed by tumor removal guided by fluorescence microscopy. The control group undergoes traditional white light microscopic tumor resection. Both groups have cranial enhanced MRI scans within 72 hours after surgery to assess the extent of tumor removal. During the study, participants are monitored for adverse events starting 4 hours before the test drug administration or surgery and continuing through the postoperative safety follow-up. Researchers track the gross total resection rate within 72 hours after surgery as the primary outcome. They also evaluate the diagnostic rate of strongly fluorescent tissue biopsy specimens within 15 days post-surgery. Participants must comply with follow-up visits and assessments throughout the trial duration.

Researchers are studying individuals who have unusual reactions to sunlight, known as photosensitivity, to understand how ultraviolet B (UVB) light affects tiny particles called microvesicle particles (MVP) released from the skin. The study aims to find out if UVB exposure increases MVP levels, whether applying a topical medicine called imipramine can block this release, and if the cream can reduce skin redness caused by UVB. This is a Phase 1 pilot study sponsored by Wright State University focused on these responses in photosensitive adults. Participants will receive different treatments on UVB-exposed skin areas of the volar forearm and back. One area will be treated with 2 grams of 4% imipramine cream, another with 2 grams of a base cream without active medicine, and a third UVB-exposed area on the back will not receive any cream. These treatments are designed to compare the effects of imipramine against no treatment and the base cream. During the study, researchers will measure changes in microvesicle particle levels and skin redness at several times: 4 hours after treatment for MVP levels and skin erythema, and also 24 hours after topical imipramine application for skin redness. Participants will provide their medical history and medication list and will be monitored for skin reactions. The total participation time covers these assessments following UVB exposure and cream application.